Evaluating Compulsive‐Like Drug‐Taking Using Signaled and Unsignaled Footshock Procedures in Male and Female Rats Self‐Administering MDPV

Abstract

A subset of rats that self‐administer synthetic cathinones, such as 3,4‐methylenedioxypyrovalerone (MDPV), develop high levels of drug intake and patterns of responding similar to the compulsive, binge‐like patterns of cathinone (e.g., “bath salts”) use reported in humans. Though high‐responder rats exhibit some behaviors thought to be related to substance use disorder, the effects of punished responding in these rats were unknown. These studies evaluated whether (1) high‐responder rats were less sensitive to footshock‐punished responding than low‐responder rats using both unsignaled and signaled footshock procedures; (2) whether sensitivity to footshock was dependent on the self‐administered dose of MDPV. Inhibition curves for unsignaled footshock (0.05‐0.9 mA, increasing across sessions) were evaluated in forty adult Sprague Dawley rats self‐administering 0.01, 0.032, and 0.1 mg/kg/infusion MDPV under a FR5 schedule of reinforcement; footshocks were paired with ~50% of drug infusions. Rats were then trained on a signaled footshock procedure, in which a change in stimulus conditions signaled that the next infusion would be paired with a footshock (intensities individualized to each rat’s IC50). Rats could avoid this footshock by withholding responding for 30‐sec. After rats learned the signaled shock procedure, inhibition curves were generated using a range of footshock intensities (0.05‐0.9 mA). High‐ and low‐responder rats were similarly sensitive to unsignaled punishment by footshock (mean IC50s‐ high‐responders: 0.30mA; low‐responders: 0.36mA). However, high‐responder rats (mean: 45mA) received significantly more total current than low‐responder rats (mean: 18mA). Compared to low‐responder rats, high‐responder rats respond more in the presence of the signal indicating impending shock and avoid a smaller proportion of shocks. This suggests high‐responder rats may be less able to adapt their behavior in response to a stimulus associated with punishment. These studies suggest that the high levels of drug‐taking observed in the high‐responder rats reflects a compulsive‐like pattern of responding, which may be related to continued use despite adverse consequence, a DSM symptom of substance use disorder.